Salmonellosis is the most frequent food-borne illness in the US. The recent emergence of multiple antibiotic-resistant S. typhimurium strains, such as definitive phage type 104 (DT104) has illustrated that the use of antibiotics will no longer combat salmonellosis effectively in the future. In order to devise alternatives to antibiotic therapy for the control or prevention of Salmonella infections, an understanding of the fundamental factors that Salmonella uses to cause infection and disease is needed. Little is known about genes allowing S. typhimurium to infect cattle, an important meat source in the US. The proposed research will characterize bovine virulence factors of S. typhimurium which will facilitate the development of improved strategies for prevention and treatment of infection. This research will also establish a new animal model for the study of human diarrheal disease caused by Salmonella. Overall project goals and supporting objectives: (1) Analysis of the adherence mechanisms which contribute to host adaptation. (2) Analysis of the role of the invasion associated type III secretion system in host-adaptation and diarrhea. Plans to accomplish project goals: The investigators have identified two virulence factors which contribute specifically to disease in cattle. One, a putative adhesin, will be characterized to determine its role in colonization of bovine intestine. The second factor is a secretion system which is specifically required to cause diarrhea in calves. They will determine the identity of the secreted proteins and study their role in causing diarrhea.